During the last two years, we were able to clarify the genetic aspect of the conversion from acute to hyperacute rejection. The conversion lacks genetic specificity so any disparity between donor and recipient may elicit it as long as it is of sufficient strength. The effector cells lack Lyt specificity. Lyt 1 as well as Lyt 2 and 3 cells will effect conversion. Experiments on T cell-depleted and nude mice suggest that the transferred cells are the actual effectors of the conversion and not merely inciters of a reaction by the recipient. The kinetics of effector cells have been studied by means of adoptive transfer. Cells from lymph nodes draining antigenic sites become transfer effective after a time period dependent on the nature of the antigenic site: after intradermal sensitization it takes 48 hrs; after skin grafting, 9 days. With either method, transfer effectiveness ceases after 5 days, unless the cells are transferred to a nonsensitized syngeneic recipient. Intraperitoneal sensitization has singularly and consistently failed to elicit transfer-effective cells. There is evidence that transfer effectiveness ceases when and because the cell donor reaches a high level of sensitization. The likely explanation rests with the relationship of delayed type hypersensitivity (DTH) to serum antibody. Cell-mediated hyperacute rejection (CMHAR) is very likely a manifestation of DTH. Serum antibody tends to block development and maintenance of DTH. Abrupt cessation of transferability after a predictable number of days may be due to the emergence of serum antibody in the primary recipient of sensitizing cells. The secondary recipient of transferred cells is not sensitized, lacks serum antibody, and is more hospitable to the transferred cells. It would explain the rapid and predictable disappearance of the "white graft" reaction subsequent to i.p. sensitization, the most intense manifestation of CMHAR. This interpretation is consistent with our irradiation data and our experience with heterotopically transplanted mouse hearts. Regarding the former, sensitization aimed at CMHAR is radio-resistant for about 6 days, whereafter sublethal irradiation abolishes the sensitization effect; presumably DTH has decreased by that time, possibly because of a rising titer of serum antibody. Regarding heterotopic heart transplantation, sensitization leading to CMHAR (of skin grafts) results in prolongation of heart survival. We do not know whether this is related to incomplete serum antibody or a totally unexpected and unexplained effect of CMHAR. (IP)